Objective To explore the establishment of a subcutaneously transplanted tumor model of hepatocellular carcinoma in mice with Qi stagnation and blood stasis syndrome. Methods Forty male C57BL/6 mice were randomly divided into 4 groups: NC group, QZXY group, Tumor group, and QZXY + Tumor group. They were categorized based on the modeling of Qi stagnation and blood stasis syndrome (7 days) combined with the modeling of subcutaneous transplantation of hepatocellular carcinoma tumor (20 days). Observations were conducted of the syndrome manifestations as well as the tumor size and weight of the mice after modeling. Results (1) Body weight: on the 7th day of modeling, the weights of the QZXY group and QZXY + Tumor group were significantly lower than that of the NC group (P<0.05). (2) Body temperature: on the 7th day of modeling, body temperature significantly decreased in the QZXY group (P<0.05), while it increased in the Tumor group (P<0.05) compared with the NC group. On the 27th day of modeling, the temperature of the QZXY + Tumor group was significantly lower than that of the NC group (P<0.05). (3) Syndrome manifestations: according to the syndrome scoring table, mice in both the QZXY group and QZXY + Tumor group exhibited Qi stagnation and blood stasis syndrome on the 7th day of modeling (P<0.05). As modeling time extended, the score of mice in the Tumor group increased with the formation of the tumor, and the score of mice in the QZXY + Tumor group was significantly higher than that of the other three groups (P<0.05). (4) Claw petechiae: the number of claw petechiae significantly increased in all three groups of modeled mice compared with the NC group (P<0.05), with the QZXY + Tumor group showing the highest number. (5) Claw r value: the r value of the claw was significantly lower in all three groups of modeled mice than that in the NC group (P<0.05). Additionally, the r value of the claw in the QZXY + Tumor group was consistently lower than that of the other three groups. (6) Open field activity: the vertical and horizontal activity of mice in the QZXY + Tumor group decreased significantly compared with that of the NC group (P<0.05). (7) Coagulation indexes: APTT, TT, and FIB were significantly increased in the QZXY + Tumor group (P<0.05 or P<0.01) compared with those in the NC group. (8) Tumor size and weight: compared with the Tumor group, the QZXY + Tumor group showed significantly increased tumor size and weight (P<0.05). Conclusions This study successfully established a subcutaneous transplanted tumor model of hepatocellular carcinoma in mice with Qi stagnation and blood stasis syndrome. The findings indicated that Qi stagnation and blood statsis syndrome may occur during the course of live cancer. Besides, the causes inducing the Qi stagnation and blood stasis syndrome will further accelerate the progression of liver cancer.